Current high throughput library preparation methods to analyze genomes and transcriptomes contain sequence information that mostly preserves the natural abundance of genes and transcripts. Typically, genomic libraries from higher eukaryotes, especially plants, contain a significant amount of repetitive DNA. Similarly, transcriptome libraries from both eukaryotes and prokaryotes largely contain cDNA sequences that are derived from a small number of abundant transcripts. Sequence information derived from ribosomal RNA (rRNA) predominate transcriptome libraries even after their removal prior to conversion to cDNA. Further, preparations of nucleic acids from eukaryotes, unless they are fractionated, contain sequences from organelles such as mitochondria and/or chloroplasts and these sequences further constitute a source of unwanted data. While useful for copy number analysis and expression profiling, the complexity of sequence information in these libraries may be a hindrance in the analysis of sequence variants and may mask information derived from low copy genes and transcripts. Therefore, there is a need for methods to reduce the complexity of libraries to aid, for example, in the discovery and analysis of low copy genes, their variants and expressed transcripts.